Unveiling Cross-communication among Brain Cells Uncovers a Fresh Approach in Alzheimer's Research
In a groundbreaking research, a study conducted by Dr. Oscar Harari and his colleagues has shed light on the interactions between brain cells in the context of Alzheimer's disease. The study, titled "Systematic analysis of cellular crosstalk reveals a role for SEMA6D-TREM2 regulating microglial function in Alzheimer's disease," was published in Science Translational Medicine.
The study utilised tissue immunostaining of human brains, single-nucleus transcriptional profiles from the Knight Alzheimer Disease Research Center and the Dominantly Inherited Alzheimer Network cohorts, and spatial transcriptomics on the human brain.
The research found that SEMA6D, a protein, colocalises with Aβ plaques and TREM2-activated microglia. Microglia are a type of brain cell that plays a crucial role in the immune system. The study suggests that the loss of SEMA6D signaling impairs microglial activation and Aβ clearance, key processes in the progression of Alzheimer's disease.
To validate this hypothesis, the study used TREM2 knockout human induced pluripotent stem cell-derived microglia and observed that SEMA6D induces microglial activation and Aβ plaque phagocytosis in a TREM2-dependent manner.
The study also identified a gene network mediating neuron-microglia cross-talk through TREM2 and neuronal SEMA6D, which is predicted to be disrupted in late Alzheimer's disease stages. Interestingly, the study found that plaque-proximal SEMA6D abundance decreased with the disease stage, which correlated with a reduction in microglial activation near plaques.
The study concludes that characterising cellular cross-talk networks can yield insights into Alzheimer's disease biology, provide additional context to understand Alzheimer's disease genetic risk, and find previously unknown therapeutic targets and pathways. This research could potentially pave the way for new treatments and a better understanding of this debilitating disease.
However, further research is needed to fully understand the role of SEMA6D in Alzheimer's disease and its potential as a therapeutic target. The exact role of Dr. Oscar Harari in this research project investigating interactions between brain cells remains unclear as there is no information available about it in the provided search results.
